Upon starting the game, the player takes control of Sulley, who is introduced to Thaddeus Bile, one of Monsters, Inc.'s new recruits, by Henry J. Waternoose III. The player is tasked with finding and obtaining Bile's manual and key card, which are essential to his training. The player then must ride the mail train to reach Boo, while avoiding being stopped by CDA agents. However, Boo soon manages to escape again, forcing Sulley to race through the rooftops of Monstropolis buildings, while avoiding being spotted by the CDA helicopter. Soon after getting ahold of Boo once more, Sulley must search in his apartment building for materials to create a disguise for Boo, so as to hide her from other employees at Monsters, Inc.
Once at Monsters, Inc., Boo escapes from Sulley's hands once again, and ends up at the garbage disposal, a very dangerous place. As such, Sulley must chase Boo, while avoiding other monsters that look similar to Boo's disguise. Sulley later must go to the Himalayas, and reach the village. Upon Sulley's return to Monsters, Inc., he must explore the huge library of closet doors, while avoiding falls. In the final level of the game, Sulley must shut down the power supply by scaring the switches, and saving Boo from the hands of the evil Mr. Waternoose.